TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25026	75301;75302;75303	chr2:178571056;178571055;178571054	chr2:179435783;179435782;179435781
N2AB	23385	70378;70379;70380	chr2:178571056;178571055;178571054	chr2:179435783;179435782;179435781
N2A	22458	67597;67598;67599	chr2:178571056;178571055;178571054	chr2:179435783;179435782;179435781
N2B	15961	48106;48107;48108	chr2:178571056;178571055;178571054	chr2:179435783;179435782;179435781
Novex-1	16086	48481;48482;48483	chr2:178571056;178571055;178571054	chr2:179435783;179435782;179435781
Novex-2	16153	48682;48683;48684	chr2:178571056;178571055;178571054	chr2:179435783;179435782;179435781
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-70
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.4242
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Q/P	None	None	0.856	N	0.515	0.376	0.294561560033	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Q/A	0.2741	likely_benign	0.2601	benign	-0.773	Destabilizing	0.209	N	0.403	neutral	None	None	None	None	N
Q/C	0.5203	ambiguous	0.4894	ambiguous	-0.137	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	N
Q/D	0.6486	likely_pathogenic	0.6067	pathogenic	-1.009	Destabilizing	0.722	D	0.291	neutral	None	None	None	None	N
Q/E	0.1147	likely_benign	0.1069	benign	-0.818	Destabilizing	0.285	N	0.339	neutral	N	0.456334265	None	None	N
Q/F	0.6852	likely_pathogenic	0.6493	pathogenic	-0.169	Destabilizing	0.818	D	0.523	neutral	None	None	None	None	N
Q/G	0.4216	ambiguous	0.4011	ambiguous	-1.207	Destabilizing	0.722	D	0.468	neutral	None	None	None	None	N
Q/H	0.2372	likely_benign	0.2235	benign	-0.943	Destabilizing	0.873	D	0.443	neutral	N	0.503050776	None	None	N
Q/I	0.3691	ambiguous	0.3468	ambiguous	0.383	Stabilizing	0.39	N	0.49	neutral	None	None	None	None	N
Q/K	0.1104	likely_benign	0.1077	benign	-0.504	Destabilizing	0.005	N	0.209	neutral	N	0.442655679	None	None	N
Q/L	0.1539	likely_benign	0.1415	benign	0.383	Stabilizing	0.166	N	0.417	neutral	N	0.502877418	None	None	N
Q/M	0.3493	ambiguous	0.3308	benign	0.695	Stabilizing	0.901	D	0.441	neutral	None	None	None	None	N
Q/N	0.4367	ambiguous	0.4107	ambiguous	-1.137	Destabilizing	0.561	D	0.297	neutral	None	None	None	None	N
Q/P	0.9111	likely_pathogenic	0.9005	pathogenic	0.028	Stabilizing	0.856	D	0.515	neutral	N	0.504743365	None	None	N
Q/R	0.1117	likely_benign	0.1082	benign	-0.596	Destabilizing	None	N	0.204	neutral	N	0.457046341	None	None	N
Q/S	0.2899	likely_benign	0.275	benign	-1.32	Destabilizing	0.345	N	0.303	neutral	None	None	None	None	N
Q/T	0.221	likely_benign	0.214	benign	-0.93	Destabilizing	0.561	D	0.394	neutral	None	None	None	None	N
Q/V	0.2642	likely_benign	0.2445	benign	0.028	Stabilizing	0.004	N	0.437	neutral	None	None	None	None	N
Q/W	0.605	likely_pathogenic	0.5495	ambiguous	-0.13	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	N
Q/Y	0.4816	ambiguous	0.44	ambiguous	0.147	Stabilizing	0.901	D	0.537	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.